amonafide in treating women with metastatic breast cancer that has progressed after previous chemotherapy

Conditions: Breast Cancer

Summary: rationale: drugs used in chemotherapy, such as amonafide, work in different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase ii trial to study the effectiveness of amonafide in treating women who have metastatic breast cancer that has progressed after previous chemotherapy.

objectives: primary * determine the time to progression in women with metastatic breast cancer who have progressed after prior chemotherapy and are now treated with amonafide. * determine the overall response rate (complete and partial response) in patients treated with this drug. * determine the safety of a phenotypically driven dosing regimen of this drug in these patients. secondary * determine the time to tumor response, duration of response, and time to treatment failure in patients treated with this drug. * determine the overall survival of patients treated with this drug. * determine the pharmacokinetic profile of this drug in these patients. outline: this is an open-label, multicenter study. patients receive amonafide iv over 1 hour on days 1-5. treatment repeats every 21 days for at least 5 courses in the absence of disease progression or unacceptable toxicity. patients with stable or responding disease may receive additional courses (beyond 5 courses) at the investigator's discretion. patients are followed at 30 days and then every 3 months. projected accrual: a total of 175 patients will be accrued for this study within 1 year.

Eligibility criteria:
disease characteristics: * histologically confirmed breast cancer * metastatic (stage iv) disease * relapsed after 1 of the following prior therapy regimens\*: * adjuvant therapy containing an anthracycline and a taxane * adjuvant anthracycline therapy followed by first-line metastatic treatment containing a taxane note: \*no relapse within 12 months of initiation of prior therapy * measurable disease by ct scan or mri * no ascites, pleural effusions, or osteoblastic bone metastases as the only site of measurable disease * refractory to hormonal anticancer therapy completed more than 4 weeks before study therapy * her2/neu positive allowed provided patient received prior trastuzumab (herceptin®) * muga or echocardiogram normal while on trastuzumab * no known history of or current brain or leptomeningeal metastases * hormone receptor status: * not specified patient characteristics: age * over 18 sex * female menopausal status * not specified performance status * ecog 0-2 life expectancy * at least 12 weeks hematopoietic * wbc at least 3,000/mm\^3 * neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * hemoglobin at least 10.0 g/dl * no clinically significant abnormal hematological parameters hepatic * bilirubin no greater than 1.5 times upper limit of normal (uln) * alkaline phosphatase no greater than 2.5 times uln (5 times uln in case of liver metastases) * ast or alt no greater than 2.5 times uln (5 times uln in case of liver metastases) renal * creatinine no greater than 1.5 times uln cardiovascular * see disease characteristics * no myocardial infarction within the past 3 months * no unstable angina pectoris * no new york heart association class iii or iv heart disease * no uncontrolled arrhythmia * no cardiac insufficiency * no uncontrolled hypertension * lvef at least 50% or at least lower limit of normal other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception 4 weeks before, during, and for at least 4 weeks after study participation * no preexisting neuropathy (motor or sensory) greater than grade 2 * no clinically significant abnormal biochemical parameters * no clinically significant active infection * no other prior malignancy except cured nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix * no other serious illness or medical condition * no psychological illness or condition that would preclude study participation * no other known condition that would preclude study participation prior concurrent therapy: biologic therapy * see disease characteristics * more than 3 months since prior trastuzumab * more than 2 weeks since prior growth factor therapy (i.e., filgrastim \[g-csf\] or sargramostim \[gm-csf\]) * no concurrent systemic anticancer immune modulators chemotherapy * see disease characteristics endocrine therapy * see disease characteristics * more than 4 weeks since prior hormonal therapy * no concurrent anticancer hormonal therapy * no concurrent chronic systemic steroids * concurrent topical or inhaled steroids for dermatological or allergy/asthma conditions allowed provided therapy was initiated prior to study enrollment * concurrent hormone replacement therapy allowed provided therapy was initiated prior to study enrollment radiotherapy * more than 30 days since prior radiotherapy * no concurrent radiotherapy directed at target lesions surgery * at least 4 weeks since prior major surgery and recovered other * more than 30 days since prior investigational new drug * more than 2 weeks since prior blood transfusion * no other concurrent systemic anticancer agents, including immunosuppressive agents * no other concurrent investigational agents * concurrent bisphosphonates allowed provided therapy was initiated prior to study enrollment

Keywords: stage iv breast cancer recurrent breast cancer